The somatosensory cortex is a highly developed region of the brain that demonstrates substantial ability to adapt to environmental changes in both young and adult animals. Although considerable research efforts have identified factors contributing to neuronal plasticity, the precise mechanisms that allow the brain to reorganize have yet to be clearly revealed. It has been known for many years, however, that young brains have a different capacity to adapt after injury or disease than adult brains. The experiments described here will attempt to identify factors that assist in our understanding of why the nervous system possesses a greater reorganizational ability during development than in adulthood. The proposed studies will evaluate the development of ferret somatosensory cortex. The ferret is an excellent animal to use for developmental study since its cerebral cortex is highly immature at birth. First, the normal development of somatosensory cortex will be assessed, followed by evaluating disrupted development produced by lesions to structures identified as being important for normal laminae of the developmental progression. i) The birthdates of neurons destined to reside in different somatosensory cortex and subjacent subplate, as well as their route of migration to the cortex, will be determined using 3H-thymidine injections. The subplate is a region of the developing neocortex that appears consequential in normal, cortical maturation and is identified as a compartment where In ingrowing afferent fiber systems "wait", and possibly interact, before proceeding into the cortex. In addition, the growth of afferent fiber populations into the somatosensory cortex will be studied in the same brains using DiI injections into the cortex, the ventrobasal thalamus, and the basal forebrain. The relationship of these fibers to the maturing cortical and subplate neurons will be analyzed. ii) The distribution of muscarinic receptor subtypes will be studied in the developing somatosensory cortex using antibodies developed against specific recombinant muscarinic receptor proteins. Muscarinic receptors are sensitive to acetylcholine, a substance that modifies neuronal responses and appears to play a significant role in the development of cortical architecture and function. iii) The affect of transecting a peripheral nerve, or a lesion of the subplate, early in life will be assessed for their impact on the organization of cortical layers, the distribution of afferent fibers populations, or the development of muscarinic receptors. I predict that both these lesions will lead to altered cortical function and anatomic organization, and that both systems play an important role in sculpting normal cortical development in the somatosensory system. In addition an understanding of the mechanisms of neural plasticity will be significant in our ability to improve recovery from cerebral vascular accident or trauma to the nervous system.